ANTIHYPERTENSIVE DRUGS

 Aims and Objectives

 Introductions
 Classification
 Propranolol
 Amlodipine
 Methyldopa
 Prazosine
 Glossary
 Terminal examination model questions
 AIMS AND OBJECTIVES
To introduce the student the drugs that affect the heart and blood vessels.
After a thorough study of this unit, the student must be able to
 Give an account of antihypertensive drugs
 Classify antihypertensive according to their mode of action
 Present the synthesis of propranolol, amlodipine, prazosine and methyldopa
 INTRODUCTIONS
Hypertension is defined as a condition in which systolic and or diastolic blood pressure
exceeds above 140/90 mm Hg. Dugs which have direct action on heart or other parts of the
vascular system, so that they modify the total output of the heart and modify the distribution of
blood to certain parts of the circulatory system and lowers the blood pressure is called as
antihypertensive drugs. These drugs are used in the treatment of hypertension. An ideal
antihypertensive drug should reduce blood pressure without any side effects.
 CLASSIFICATION
These are classified into following types
 Angiotensin converting enzyme (ACE) inhibitors:

Captopril Enalapril
 Angiotensin AT1 antagonist:
 O COOH
CH3
CH CH
H3CH2CH2CH2C N
CH3
CH2

HN N
N
N

Losartan Valsartan
 Calcium channel blockers:

Cl
H3COOC COOC2H5

H3C N CH2OCH2CH2NH2
H
Nifedipine Amlodipine

Diltiazem

 Sympatholytics:
o β-adrenergic blockers:

Propranolol Metoprolol
 Atenolol
o β-adrenergic blockers with α1 receptor antagonist:
H3CO

O CH2 CH CH2 NH CH2 CH2 O

OH

N
H
Carvediol
o α1- adrenergic blockers:

Prazosin Terazosin
o Central sympatholytics:

Methyldopa Clonidine
 Ganglionic blocking agents:

Hexamethonium Pentolinium
 Pempidine
 Vasodialators:

Hydralazine Minoxidil Diazoxide

 Diuretics:

Furosemide Hydrochlorothiazide
 Adrenergic neuron blockers: reserpine, guanethidine
 PROPRANOLOL
Propranolol, 1-(iso-propylamino)-3-(1-naphthyloxy)-2-propanol (11.4.1.5), is synthesized
as below

MOA: Propranolol lowers blood pressure by competitively inhibiting β1 (cardiac) and β2

(vascular) receptor. It reduces contractility of myocardium (negative inotropic), decreases heart
rate (negative chronotropic), lowers cardiac output, inhibits the release of renin, and lowers
sympathetic release from the central nervous system.
Uses: Propranolol is used in treatment of angina, extrasystole, superventricular
arrhythmia, ventricular tachycardia, migraines and pheochromocytoma. It also is used in the
postanginal phase of myocardial infarctions.
 AMLODIPINE
Amlodipine, 3-Ethyl-5-methyl-2-(2-aminoethoxymethyl)-4-(2-chlorophenyl)-6-methyl-1,4-
dihydropyridine-3,5-dicarboxylate, is synthesized as below

MOA: Calcium is involved in myocardial contraction and constriction of vascular

smooth muscle. Amlodipine acts as antagonist of L type (Ligand gated) calcium channel and
causes relaxation of smooth muscle of vessels, dilates coronary and peripheral arteries, and
reduces peripheral resistance, arterial pressure, and the oxygen supply to the heart.
Uses: Amlodipine is used for preventing and relieving angina pectoris attacks, for
hypertension, and as an ingredient in combination therapy for chronic cardiac insufficiency.
 METHYLDOPA
Methyldopa, 3-(3,4-dihydroxyphenyl)-2-methylalanine, is synthesized as below

MOA: Methyldopa is a α-methoxylated derivative of levodopa that is decarboxylated and

hydroxylated into methylnoradrenaline (methylnorepinephrine), which acts as an agonist on the
α2 receptor. It reduces overall peripheral vascular resistance and heart work. At larger dose it also
inhibits the enzyme dopa decarboxylate in brain and periphery, which leads to reduction of
noradrenaline synthesis.
Uses: It is prescribed for arterial hypertension and hypertensive crises.
 PRAZOSIN:
Prazosin, 1-(4-amino-6,7-dimethoxy-2-quinazolinyl)-4-(2-furoyl)-piperazine is synthesized as
below

MOA: Prazosin is a α1 antagonist; it causes peripheral vasodialation by inhibiting post synaptic

α1 receptor in vascular smooth muscle.
Uses: Prazosin is used for treating mid-to-moderate hypertension.
 Non pharmacological methods for the treatment of hypertension:
Hypertension is one of the most preventable contributors to disease and death. It is the most
common condition treated in primary care and can lead to myocardial infarction, stroke,
renal failure, and death if not detected early and treated appropriately.
nonpharmacologic strategies such as healthy diet, weight control, and regular exercise is
helpful in the management of blood pressure.
Diet: A diet with a high intake of vegetables, fruits, and whole grains is recommended.
Other recommendations include consuming low-fat dairy products, poultry, fish, legumes,
non-tropical vegetable oils, and nuts; and limiting intake of sweets, sugar-sweetened
beverages, and red meat.
Sodium Intake: There is strong and consistent evidence that reducing sodium intake
reduces blood pressure. Adults who would benefit from lowering blood pressure should be
advised to limit their sodium intake to no more than 2,400 mg per day (about 1 teaspoon of
table salt).
Physical Activity and Weight Loss: Adults should engage in moderate to vigorous aerobic
physical activity three or four times per week for an average of 40 minutes per session to
lower blood pressure. Most health benefits occur with at least 150 minutes per week of
moderate-intensity physical activity, such as brisk walking.
Smoking Cessation: Cigarette smoking is the leading preventable cause of death and
significantly increases the risk of cardiovascular disease. Smoking causes an immediate
increase in sympathetic nervous activity, which in turn increases myocardial oxygen demand
through increased blood pressure, heart rate, and myocardial contractility. A study found that
quitting smoking after a heart attack or cardiac surgery decreases a patient's risk of death by
more than 33% over five years.
 GLOSSARY
Hypertension: abnormally high blood pressure.
Migraine: a recurrent throbbing headache that typically affects one side of the head and it is
often accompanied by nausea and disturbed vision.
Tachycardia: abnormally rapid heart rate.
Pheochromocytoma: it is a neuroendocrine tumor of the medulla of the adrenal glands.
 TERMINAL EXAMINATION MODEL QUESTIONS
 1. What are antihypertensive agents? Explain in detail. Classify the antihypertensive
agents by giving suitable examples .Give the synthesis of any two antihypertensive drugs
of your choice
2. Explain in detail about antihypertensive agents. Give the synthesis of propranolol.
3. Write a note on vasodilators.
 BOOKS FOR FURTHER READING
 Wilson and Gisvold, Text book of organic, Medicinal and Pharmaceutical Chemistry.
 A Text book of medicinal chemistry (Synthetic and Biochemical Approach) vol. I& II by
SN Pandeya.
 Medicinal chemistry by Ashutosh Kar.
 Synthesis of Essential drugs by R.S.Vardanyan and V.J.Hurby.